August 9, 2011CirculationOpen Access

Striking In Vivo Phenotype of a Disease-Associated Human SCN5A Mutation Producing Minimal Changes in Vitro

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Population

Chinese hamster ovary cells, tsA201 cells, and genetically modified mice. Also includes one patient with…

Comparison

D1275N (DN) human SCN5A cDNA allele vs Full-length wild-type (H) human SCN5A cDNA allele

Design

Preclinical

Authors

HWHiroshi WatanabeKurume University TYTao YangTang Du Hospital DSDina Myers StroudVanderbilt University Medical Center

Discussion

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Implication

Supports in vivo pathogenicity of D1275N SCN5A despite normal in vitro function; hypothesis-generating for human cardiomyopathy without altering practice.

Structured PICO

Population

Chinese hamster ovary cells, tsA201 cells, and genetically modified mice (Scn5a locus modified to knock out the mouse gene and insert human SCN5A cDNAs). Also includes one patient with atrial flutter, atrial standstill, conduction disease, and sinus node dysfunction.

Intervention

D1275N (DN) human SCN5A cDNA allele

Comparator

Full-length wild-type (H) human SCN5A cDNA allele

Outcome

Peak sodium current amplitudes and in vivo cardiac phenotype (conduction, arrhythmias, cardiomyopathy)surrogate

The D1275N SCN5A mutation, despite showing near-normal function in vitro, is a pathological mutation in vivo that reduces cardiac sodium current and causes conduction slowing, arrhythmias, and dilated cardiomyopathy.

Cite This Study

Watanabe et al. (2011) studied this question.

synapsesocial.com/papers/6a7ae222e357fbdac589b2ee https://doi.org/10.1161/circulationaha.110.987248

Topics

Cardiac device therapy

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Implication

Supports in vivo pathogenicity of D1275N SCN5A despite normal in vitro function; hypothesis-generating for human cardiomyopathy without altering practice.

Striking In Vivo Phenotype of a Disease-Associated Human SCN5A Mutation Producing Minimal Changes in Vitro

Discussion

Member takes

Implication

Structured PICO

Cite This Study

Topics

Striking In Vivo Phenotype of a Disease-Associated Human SCN5A Mutation Producing Minimal Changes in Vitro

Discussion

Member takes

Implication

Structured PICO

Cite This Study

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